Black Tongue: A Rare Presentation of Rhupus Syndrome

Black tongue is a benign condition typically caused by the overgrowth of dead skin cells, resulting in elongated papillae and a hairy appearance. Other factors contributing to this condition include inadequate oral hygiene, a soft diet, and staining from bacteria, food, yeast, and other substances. It may cause symptoms such as bad breath, a metallic taste in the mouth, and an unsightly black hairy-looking tongue. Here, we present a case of a 30-year-old female who came to our hospital complaining of bad breath and a black tongue for the past month. She had previously taken antibiotics at the primary care medical center, but there was no improvement. We then prescribed her fluconazole, an antifungal medication, for the next two weeks. After two weeks, she returned with a slightly improved tongue color. Further investigation revealed a history of abortion and mild intermittent joint pains, for which she had been self-medicating with over-the-counter acetaminophen. A complete work-up led to the discovery of positive anti-cyclic citrullinated peptide (anti-CCP) antibodies, anti-double-stranded (anti-DS) DNA antibodies, and ANA, leading to the diagnosis of Rhupus Syndrome, an overlap of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).


Introduction
Rhupus syndrome, coined by Peter Schur in 1971, refers to a rare condition where patients meet the criteria for both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) [1]. In Rhupus syndrome, SLErelated features are generally mild and primarily involve the skin, mucosa, and blood [2]. While there are no specific diagnostic criteria for Rhupus syndrome, the established standards for diagnosing SLE (SLICC-2012) and RA (ACR/EULAR-2010) are used. Additionally, joint surface erosion, high levels of RA factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies, ANA, and anti-double-stranded (anti-DS) DNA are considered in identifying Rhupus syndrome [3]. Due to the rarity of this condition, limited information is available regarding its pathophysiology, prevalence, natural history, immunological characteristics, and radiological findings. The exact cause and triggers of Rhupus syndrome remain largely unknown, with some studies suggesting the involvement of immunological, hormonal, genetic, and environmental factors [4]. Given that treatment options and outcomes differ for Rhupus syndrome compared to RA or SLE alone, it is vital to categorize patients accordingly [5]. Notably, the occurrence of black hairy tongues, typically associated with factors such as poor oral hygiene, certain medications, and smoking, has not been previously described in either RA or SLE [6].

Case Presentation
Our patient is a 30-year-old female who does not smoke or consume alcohol. She follows a vegetarian diet and works as a homemaker. She was referred to our hospital from a primary care center due to her complaint of tongue blackening, which she had been experiencing for the past two to three weeks. Before seeking medical attention, she had tried to improve her oral hygiene, used mouth rinses and washes, and even underwent antibiotic therapy. Aside from the tongue blackening, the patient did not report any other complaints. Figure 1 illustrates the appearance of the blackened tongue when the patient initially presented to us.

FIGURE 1: Appearance of the blackened tongue before treatment
We assured her that the blackening of her tongue was a benign condition. The doctor prescribed her antifungal medication for the next two weeks and instructed her to return for a follow-up visit after that time. However, there was little to no improvement in her symptoms and only a minimal change in the color of her tongue. Figure 2 illustrates the negligible difference in color after approximately two weeks of antifungal treatment.     Based on her clinical presentation and test results, we initiated treatment with hydroxychloroquine, thyroxine, methotrexate, and methylprednisolone. Additionally, we prescribed vitamin D and calcium supplements for two months. Figure 3 illustrates the color change observed in her tongue after two months of the prescribed treatment.

Discussion
Rhupus syndrome, a rare condition, represents an overlap between SLE and RA, characterized by distinct clinical features and laboratory findings. Evidence supporting the diagnosis of Rhupus syndrome in patients with SLE and RA is limited [7]. Doctors usually treat Rhupus syndrome with steroids and DMARDs, medications commonly used for RA and SLE. When organ systems are affected, doctors may prescribe biological agents and immunosuppressants. However, the term "Rhupus syndrome" remains controversial due to the opposing immunopathological processes involved in SLE (characterized by abnormal activation of Th2 cytokines) and RA (involving Th1 response) [8]. Consequently, the incidence of this overlap between RA and SLE in arthritis patients is low, ranging from 0.01% to 0.2%. Some authors argue that Rhupus syndrome represents severe articular involvement in lupus rather than a mere overlap of SLE and RA [9].
Rhupus syndrome exhibits mild features associated with SLE, such as hematological abnormalities and skin and mucosal involvement. The patient presented with decreased hemoglobin, reduced white blood cell count, platelets, and intermittent oral ulcers. Elevated levels of inflammatory markers were observed, consistent with the high titers found in Rhupus patients. Our case also exhibited high levels of RA factor and anti-CCP antibodies, along with elevated ANA and anti-DS DNA antibodies [10]. The incidence of malar rash, hemolytic anemia, and involvement of the neurological and renal systems is lower in Rhupus syndrome compared to SLE. Rhupus syndrome rarely presents with nephrotic syndrome and renal insufficiency. The administration of methylprednisolone pulse therapy and initial corticosteroid dosages are typically lower in Rhupus syndrome compared to SLE flares (SLEDAI scoring is used to assess disease activity in SLE).
A study revealed an increased frequency of HLA-DR1 and HLA-DR2 alleles in patients with Rhupus syndrome [11,12]. Additionally, some authors have suggested that rheumatoid nodules in SLE patients may increase the risk of developing Rhupus syndrome [12]. Moreover, researchers have proposed that anti-CCP antibodies play a significant role in SLE patients with an elevated risk of developing erosive arthritis. These antibodies are thought to contribute to the clinical features and overlap of SLE with RA, referred to as Rhupus syndrome [13]. Radiological investigations have shown juxta-articular bone demineralization and joint erosion, which are part of the diagnostic criteria for RA.
Despite our patient experiencing mild joint pains and inconclusive x-ray results, we took proactive measures by prescribing methotrexate and folic acid. In her case, we based this decision on the elevated levels of RA factor and anti-CCP antibody [14].